EXCEED THE. SPACE PROVIDED. Autism is a serious neurodevelopmental disorder characterized by deficits in communication, abnormal social interactions, and rigid or repetitive interests and behaviors. Although there is strong evidence of an important genetic contribution to the cause of autism, the isolation of specific genetic defects that cause autism has been difficult. We plan to pursue two complementary avenues to search for autism susceptibility genes. First, we will conduct linkage analysis on a set of 150 nuclear family units collected and assessed for this project. Ascertained through a proband with autism, immediate and, when available, extended family members will be characterized by a battery of instruments that examine the domains of language ability, social relatedness, and repetitive and rigid/compulsive behavior. Each of these domains has demonstrated heritability, and impariments in these domains are found at increased rates among non-autistic relatives of probands with autism. Our recent genetic linkage study on specific language impairment (SLI) suggests that at least one susceptibility locus is shared between SLI and autism. We plan to calculate the heritability of the items in our test battery in our sample, and select the most heritable for use in linkage analysis. We will use a two-stage design, completing a full 9 cM density genome scan on the first 75 families, genotyping the remaining families at loci producing suggestive linkage results. The entire sample will be used for fine-mapping of any highly suggestive or significant linkage results. The second strategy to search for autism susceptibility genes will be to conduct large-scale association analyses using trios (proband with autism and two parents) from the families collected for this project, as well as the collections from AGRE, the NIMH Human Genetics Initiative samples and the Coriell Autism Resource samples. We anticipate approximately 850 trios will be suitable and available for use. As association methods have power to detect genetic effects that may be poorly detected by linkage, we will use this sample to investigate regions that have demonstrated suggestive linkage to autism or language phenotypes in our work and the work of others.